Recent reports have suggested that opioid peptides may be involved in renal water excretion. The present in vivo experiments, therefore, were undertaken to determine the effect of opioid peptides on the osmotic and nonosmotic release of arginine vasopressin (AVP) in the conscious rat. Experimental animals were infused intravenously with naloxone (20 μg/kg per min) or oxilorphan (40 μg/kg per min), chemically dissimilar opioid antagonists. Control rats were infused with normal saline, the vehicle for the opioid antagonists. In all three groups the osmotic release of AVP was examined during an acute hypertonic saline (3%) infusion (2 ml/100 g body wt). The antidiuresis following the hypertonic saline infusion was significantly attenuated in naloxone- and oxilorphan-treated rats, as the peak urinary osmolality (Uosm) rose to 581.4±22.4 and 558.2±27.6 mosmol/kg H2O in naloxone- and oxilorphan-treated rats as compared with the value in control rats of 735.3±24.2 mosmol/kg H2O (both P < 0.001 vs. control). At the same time the plasma AVP levels of 5.4±1.3 and 5.2±1.1 pg/ml in naloxone- and oxilorphan-treated rats, respectively, were significantly lower than the plasma AVP in control rats of 16.9±2.5 pg/ml (P < 0.001). In another three groups of rats the nonosmotic release of AVP was examined during hypovolemia induced by intraperitoneal 6% dextran (1.8 ml/100 g body wt). Following intraperitoneal administration of dextran the peak Uosm of 703.0±87.8 and 734.8±99.1 mosmol/kg H2O in naloxone- and oxilorphan-treated rats, respectively, was significantly less than the value in control rats of 1,169.3±135.5 mosmol/kg H2O (both P < 0.02 vs. control). A comparable decrease in blood volume of 13% occurred in all three groups of animals. During the dextran administration plasma AVP levels in naloxone- and oxilorphan-treated rats increased to 4.3±1.0 and 6.0±2.0 pg/ml, respectively; both of these values were significantly lower than the plasma AVP of 12.9±1.4 pg/ml in control rats (P < 0.02). The effect of opioid antagonists to impair the osmotic and nonosmotic release of AVP occurred in the absence of differences in mean arterial pressure, glomerular filtration rate and the renal response to AVP. These results, therefore, indicate that opioid peptides are involved in renal water excretion primarily by modulating the central release of AVP.
San-E Ishikawa, Robert W. Schrier